Detection of epigenetic effects of citrinin using a yeast-based bioassay
- 12 Downloads
The present study investigated the effects of citrinin (CIT) on a yeast-transformed human DNA methyltransferase (DNMT) associated with flocculation that can be inhibited by epigenetic mutagens. CIT (0.5–2 μmol/L) inhibited the flocculation levels of yeast transfected with DNMT-genes (DNMT yeast) and the reporter gene activity of FLO1, which has been associated with flocculation. In contrast, the same concentrations of CIT had little effect on reporter activity under the control of a less methylation-sensitive FLO1 promoter. It was also shown that bacterial DNMT activity could be inhibited in the presence of CIT (4 and 40 μmol/L). These results show that CIT has inhibitory activity of DNMT, suggesting that the cytotoxicity of CIT may be involved in epigenetic mutagenicity.
KeywordsCitrinin Epigenetic mutagen Yeast DNA methyltransferase
This work was supported by JSPS KAKENHI Grant Number 18K11661 and a Health and Labor Sciences Research Grant.
Compliance with ethical standards
Conflict of interest
- Ashby J, Tennant RW (1991) Definitive relationships among chemical structure, carcinogenicity and mutagenicity for 301 chemicals tested by the US NTP. Mutat Res Rev Mutat Res 257:229–306Google Scholar
- Baylin SB, Jones PA (2011) A decade of exploring the cancer epigenome—biological and translational implications. Nat Rev Clin Oncol 11:726Google Scholar
- Chevalier S, Roberts RA (1998) Perturbation of rodent hepatocyte growth control by nongenotoxic hepatocarcinogens: mechanisms and lack of relevance for human health. Oncol Rep 5:1319–1346Google Scholar
- Flajs D, Peraica M (2009) Toxicological properties of citrinin. Arch Ind Hyg Toxicol 60:457–464Google Scholar
- IARC (1987) Monographs on the evaluation of carcinogenic risks to humans: overall evaluations of carcinogenicity: an updating of IARC monographs. International Agency for Research on Cancer, Lyon, pp 1–403Google Scholar
- Knasmuller S, Cavin C, Chakraborty A, Darroudi F, Majer BJ, Huber WW, Ehrlich VA (2004) Structurally related mycotoxins ochratoxin A, ochratoxin B, and citrinin differ in their genotoxic activities and in their mode of action in human-derived liver (HepG2) cells: implications for risk assessment. Nutr Cancer 50:190–197CrossRefGoogle Scholar
- Petkova-Bocharova T, Castegnaro M, Michelon J, Maru V (1991) Ochratoxin A and other mycotoxins in cereals from an area of Balkan endemic nephropathy and urinary tract tumours in Bulgaria. IARC Sci Publ:83–87Google Scholar